The aim of this proposed research is to further investigate the factors that modify beta-galactosidase activity in human tissues. There are two human genetic diseases in which deficiencies of specific beta-galactosidase activities are observed. These include the GM1 gangliosidoses and Krabbe's disease (or globoid cell leukodystrophy). In addition to these diseases in which the deficiency of a specific beta-galactosidase is the primary enzymaic lesion, there are at least six other fatal genetic diseases in which a deficiency of beta-galctosidase is observed in one or more tissues. This includes liver from patients with the Hurler, Hunter and Sanfilippo syndromes and Mucolipidoses II and III, fibroblast cultures from Mucolipidoses II and III and glycoprotein neuraminidase deficiency and leukocytes from certain patients with neuraminidase deficiency. These observed beta-galactosidase deficiencies are thought to be secondary to some other primary enzymatic lesion. Using purified, partially purified and unpurified human beta-galactosidases the effect of various storage products will be investigated. Do these secondary deficiencies of beta-galactosidase affect the degradation of beta-linked galactose-terminal glycoproteins, glycolipids and oligosaccharides? Using a variety of natural substrates for these beta-galactosidases the effects will be measured. Beta-galactosidase appears to be particularly sensitive to modification, and beta-linked galactose is usually found near the termini of most glycoproteins and gangliosides. This could indicate some need for the control of these enzymes' activities. Using frozen samples of liver, spleen and brain, as well as blood and cultured skin fibroblasts from the above mentioned patients (plus controls) the properties of human beta-galactosidases will be studied. The findings could indicate an important role for these enzymes in maintaining normal cell growth and development.